Hypercapnic acidosis transiently weakens hypoxic pulmonary vasoconstriction without affecting endogenous pulmonary nitric oxide production

Abstract

Hypercapnic acidosis often occurs in critically ill patients and during protective mechanical ventilation; however, the effect of hypercapnic acidosis on endogenous nitric oxide (NO) production and hypoxic pulmonary vasoconstriction (HPV) presents conflicting results. The aim of this study is to test the hypothesis that hypercapnic acidosis augments HPV without changing endogenous NO production in both hyperoxic and hypoxic lung regions in pigs. Sixteen healthy anesthetized pigs were separately ventilated with hypoxic gas to the left lower lobe (LLL) and hyperoxic gas to the rest of the lung. Eight pigs received 10% carbon dioxide (CO(2)) inhalation to both lung regions (hypercapnia group), and eight pigs formed the control group. NO concentration in exhaled air (ENO), nitric oxide synthase (NOS) activity, cyclic guanosine monophosphate (cGMP) in lung tissue, and regional pulmonary blood flow were measured. There were no differences between the groups for ENO, Ca(2+)-independent or Ca(2+)-dependent NOS activity, or cGMP in hypoxic or hyperoxic lung regions. Relative perfusion to LLL (Q (LLL)/Q (T)) was reduced similarly in both groups when LLL hypoxia was induced. During the first 90 min of hypercapnia, Q (LLL)/Q (T) increased from 6% (1%) [mean (standard deviation, SD)] to 9% (2%) (p < 0.01), and then decreased to the same level as the control group, where Q (LLL)/Q (T) remained unchanged. Cardiac output increased during hypercapnia (p < 0.01), resulting in increased oxygen delivery (p < 0.01), despite decreased PaO(2) (p < 0.01)(.) Hypercapnic acidosis does not potentiate HPV, but rather transiently weakens HPV, and does not affect endogenous NO production in either hypoxic or hyperoxic lung regions.